Kostmann’s Disease and HCLS1-Associated Protein X-1 (HAX1)

Abstract

Severe congenital neutropenia (SCN), originally described by the Swedish pediatrician Rolf Kostmann, constitutes a heterogeneous disorder associated with a dramatic decrease of peripheral neutrophil granulocytes. Patients suffer from life-threatening bacterial infections unless treated by recombinant human granulocyte colony stimulating factor (G-CSF) or allogeneic hematopoietic stem cells. This review is focused on the SCN variant caused by mutations in HCLS1 Associated Protein X-1 (HAX1) (SCN3, "Kostmann Disease"). HAX1 is a ubiquitously expressed protein with pleotropic functions, including control of cellular viability, migration, and cancer progression. Even though scientific evidence on the molecular mechanisms regarding HAX1 accumulates, no unified picture has emerged. This review highlights historical milestones and our current understanding of SCN related to mutations in HAX1.

Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

“…The lack of functional HAX-1 protein interrupts the regulation of apoptosis, leading to premature death of neutrophils. A lack of neutrophils causes recurrent infections, inflammatory episodes, and other immune problems in patients with SCN [11, 12]. Our patient had many superficial abscesses on his scalp, which caused scalp peeling (Figure 1).…”

Nhân một trường hợp giảm nặng bạch cầu hạt trung tính do đột biến mới ở gen HAX1

“…Khi gen HAX1 đột biến sẽ tạo ra các protein HAX1 không có chức năng vì vậy các tế bào BCHTT sẽ chết sớm hơn dẫn đến giảm số lượng BCHTT trong máu ngoại vi. Số lượng BCHTT giảm nặng làm bệnh nhân thường xuyên bị nhiều đợt nhiễm trùng nặng, tái diễn ảnh hưởng đến sự phát triển thể chất cũng như chất lượng cuộc sống [12], [13]. Bệnh nhân của chúng tôi có rất nhiều ổ áp-xe trên da đầu làm do da đầu luôn luôn bị sưng nề đỏ (Hình 1).…”

Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review

“…In 1950, Rolf Kostmann first described ‘hereditary agranulocytosis’, or severe congenital neutropenia (SCN), characterized by an early onset of recurrent bacterial and fungal infections of the mouth, umbilical stump, skin, gastrointestinal tract, bones, lungs and lymph nodes 2 …”

“…In 1950, Rolf Kostmann first described 'hereditary agranulocytosis', or severe congenital neutropenia (SCN), characterized by an early onset of recurrent bacterial and fungal infections of the mouth, umbilical stump, skin, gastrointestinal tract, bones, lungs and lymph nodes. 2 Although pathogenic variants in ELANE are the most common genetic aetiology of autosomal dominant (AD) SCN, several others have been described in the last 2 decades: X-linked WAS gain of function (GOF); autosomal recessive (AR) HAX1, GFI1, CSF3R and G6PC3 loss of function (LOF) and AD TCIRG1 haploinsufficiency. The molecular cause is unknown in about 30% of patients with SCN.…”